Vinyl phosphine oxide, synthesis

Organozincs generated under similar conditions have been shown to add to optically active vinyl phosphine oxides with retention of configuration at phosphorus [63] (Scheme 8). In this case a 1 1 zinc/copper couple was employed to activate the zinc. The one-pot reaction proceeded best with tertiary or secondary alkyl halides. The resulting phosphine oxides are used as chiral ligands for catalysts in asymmetric synthesis and were previously only available by reaction with the analogous cuprate [147] since conjugate addition of simple alkyl halides normally results in polymerisation. 

The preparation of unsaturated phosphonates and phosphine oxides represents another class of reagents that are extensively used in organic synthesis. For example, allylic phosphonates are commonly employed in the preparation of dienes and polyenes via Horner-Emmons olefmation. Vinyl phosphonates have numerous uses as both synthetic intermediates" and bioactive compounds. 

Synthesis of (-I-) calanolide A (Scheme 8-11) was achieved by enzyme catalyzed resolution of the aldol products ( )-53. Compound 7 with acetaldehyde by aldol reaction in the presence of LDA/TiCU stereoselectively produced a mixmre of ( )-53 and ( )-54 (94% yield), the ratio of which was 96 4. ( )-53 was then resolved by lipase AK-catalyzed acylation reaction in the presence of tert-butyl methyl ether and vinyl acetate at 40 °C to obtain 41% yield of (+)-55 and 54% yield of the acetate (—)-56. Mitsunobu cyclization of (+)-55 in the presence of tri-phenylphosphine and dielthyl azodicarboxylate afforded 63% yield of (-l-)-43 with 94% ee as determined by chiral HPLC. Luche reaction on (+)-43 with CeCla 7H2O and triphenyl phosphine oxide and NaBH4 in the presence of ethanol at 30 °C gave the crude product. It was purified by column chromatography on silica gel to give 78% yield of a mixture containing 90% of (+)-calanolide A and 10% (+)-calanohde B, which were further separated by HPLC. 

The cyclohexanone (S3), an intermediate for the synthesis of thromboxane antagonists, has been prepared by a combination of phosphine oxide- and phosphonium ylide-based olefinations.30 Reaction of the lactone (50) with methoxymethyldiphenylphosphine oxide anion gave a poorly characterized adduct (presumably (51)) which on reduction with sodium borohydride, followed by treatment with sodium hydride gave the vinyl ether (52) in 80% overall yield from (SO) (Scheme 8). Further modification gave the required cyclohexanone (53). 

The use of diphenylcyanomethylphosphine oxide is effective for the synthesis of ( )-a,3-unsaturated nitriles. ° Phosphine oxides can bis used to synthesize a variety of functionalized alkenes, including vinyl ethers (215 equation 51), ° vinyl sulfides (217 equation 52), ° allylic amines (219) and amides (equation 53), " ketene acetals (221 equation 54) and ketene thioketals (223 equation In the examples of a-thio substitution, the alkenes are formed directly. 

In 1,2-alkylative carbonyl transpositions where the carbonyl group moves forward into the newly added fragement, e. g. 63 - 64, the reagent behaves as an acyl anion equivalent. We have seen one example of this in the synthesis of the occidentalol intermediate 8. Phosphine oxides with OR or SR substituents on the a-carbon 65 are ideal reagents for this process as the Horner-Wittig reaction gives vinyl compounds which can be hydrolysed to 64. 

Phosphine oxide anions are often superior to ylids in olefmation reactions, and the anion of 68, made with lithium di-isopropyl-amide (LDA), has none of the disadvantages of the ylid 67. We have made 41 a range of vinyl ethers 70 this wayc, and as part of a synthesis of stiychnos alkaloids43, we were able41 to convert the acyl indole 71 into the aldehyde 72... 

The titanium-mediated intramolecular radical vinylations of oxirane was first reported to yield alkylidene pyrrolidines 488 via the radical (3-elimination of phosphinoyl radical. The reactions of phosphine oxide precursors 487 with a stoichiometric amount of Cp2TiQ2 were carried out at room temperature using powdered manganese as reductant, from which pyrrolidines 488 were obtained in 57-82% yields (Scheme 4.146). The procedure for the synthesis of phosphine oxide precursors 487 is also shown in Scheme 4.146. 

Methoxyallene has previously been used to prepare acetylenes via its reaction with Grignard reagents, in the presence of copper(i) halides.The use of preformed dialkylcuprates, however, gave the vinyl ethers instead. The E Z ratio varied with the substituent but it is difficult to explain why the difference is observed.Methoxyallene has also been converted into its vinyl anion and used in the synthesis of dihydrofurans and furans in an analogous way to ordinary vinyl ethers.Similarly allenic cuprates have been prepared and used in the synthesis of allenes and allenic pheromonessome examples are outlined in Scheme 58. The addition of lithium dimethylcuprate to allene phosphine oxides and allenic ketones was interpreted in terms of a 1,2- rather than a 1,4-addition process, in contrast to a/3-unsaturated... 

Treatment of the alkyne with elemental iodine and a secondary phosphine oxide is a particularly attractive approach to the synthesis of vinyl iodides with Markovnikov selectivity [181]. An attractive entry point for this chemistry would he to convert the alkyne into a vinylboronate followed by the addition of iodine under basic conditions to afford the vinyl iodide [177]... 

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